Project Summary/Abstract Childhood adversity exposure is linked to recurrent and treatment resistant depression across the lifespan. Childhood adversity is also associated with exaggerated inflammatory responses to stress. Acute inflammatory responses can induce the behavioral phenotype for depression, including reduced motivation for rewards and enhanced sensitivity to threat. In this study, we aim to determine the association between childhood adversity and behavioral responses to acute psychological stress. We also aim to characterize the association between childhood adversity and inflammatory responses to stress. Finally, we aim to test whether the magnitude of inflammatory responses to acute stress mediate the behavioral response to threat. We hypothesize that youth exposed to childhood adversity will demonstrate greater increases in threat sensitivity, reward motivation, and markers of inflammation following acute psychological stress. Further, we hypothesize that inflammatory responses to stress will mediate changes in behavior in response to acute stress. We will recruit a sample of 90 adolescents (ages 12-15) exposed to high (4+ adverse childhood events) and low (0-3 adverse childhood events) adversity. During a laboratory visit, youth will complete several behavioral measures of reward motivation and threat sensitivity, participate in an acute psychological stress paradigm (TSST-C), and then complete measures of reward motivation and threat sensitivity 60 minutes after stress initiation. Throughout this laboratory assessment, we will collect blood and saliva to measure systemic, cellular, and intracellular markers of inflammation. We anticipate that data from this study will support our hypothesis that childhood adversity is associated with exaggerated behavioral and inflammatory responses to stress. Completion of this study will identify three modifiable risk factors (threat sensitivity, reward motivation, inflammation) for depression in at risk youth, and support a program of research examining cognitive and behavioral strategies that may mitigate these effects.